"A.I.C.O. -Incarnation-" is set in a near-future Japan, where a catastrophic event known as the "Burst" has devastated the Kurobe Gorge region. The Burst was caused by an out-of-control artificial life form called "Matter," which consumes and assimilates organic and inorganic materials, spreading uncontrollably. The government has quarantined the area, and a research facility, the Primary Point, lies at the epicenter of the disaster. The story centers on Aiko Tachibana, a high school student who lost her family in the Burst and now lives with her friend Yuya Kanzaki and his family. Aiko suffers from amnesia and has no recollection of the events surrounding the Burst.

Two years after the disaster, a mysterious transfer student, Yuya Kanzaki, reveals to Aiko that her body is not entirely human. She is a "Dummy," a synthetic being created to house the consciousness of the original Aiko, who is still alive and trapped within the Primary Point. The original Aiko is the key to stopping the Burst, as her body contains the "Core," a unique entity capable of controlling the Matter. Yuya, who is actually a member of a secretive organization called "Divers," proposes a mission to infiltrate the quarantined zone, rescue the original Aiko, and destroy the Core to halt the spread of Matter.

Aiko reluctantly agrees to join the mission, accompanied by a team of Divers, including the skilled leader Haruka Seri, the resourceful Isao Inaba, and the tech-savvy Susumu Kurose. As the team ventures deeper into the quarantined zone, they encounter hostile Matter creatures and uncover unsettling truths about the Burst and their own identities. Aiko struggles with her dual existence as a Dummy and grapples with the ethical implications of her creation. The team also faces internal conflicts, as some members have personal stakes in the mission that threaten to derail their objectives.

The narrative explores themes of identity, humanity, and the consequences of scientific experimentation. As the team progresses, they learn that the Burst was not an accident but the result of unethical human experiments conducted by the research facility. The original Aiko, whose consciousness is linked to the Core, holds the power to either save or destroy humanity. The story builds toward a climactic confrontation at the Primary Point, where Aiko must confront her original self and make a choice that will determine the fate of the world.

The series balances action, mystery, and emotional depth, with a focus on the moral dilemmas faced by its characters. The plot is driven by the tension between humanity's pursuit of scientific advancement and the potential for catastrophic consequences. The characters' motivations and relationships are central to the narrative, as they navigate the blurred lines between human and artificial life. "A.I.C.O. -Incarnation-" presents a thought-provoking exploration of the ethical boundaries of science and the nature of existence.